As temperatures decrease in autumn, vegetation of temperate and boreal ecosystems increases its tolerance to freezing. This process, known as hardening, results in a set of physiological changes at ...the molecular level that initiate modifications of cell membrane composition and the synthesis of anti-freeze proteins. Together with the freezing of extracellular water, anti-freeze proteins reduce plant water potentials and xylem conductivity. To represent the responses of vegetation to climate change, land surface schemes increasingly employ "hydrodynamic" models that represent the explicit fluxes of water from soil and through plants. The functioning of such schemes under frozen soil conditions, however, is poorly understood. Nonetheless, hydraulic processes are of major importance in the dynamics of these systems, which can suffer from, e.g., winter "frost drought" events.
Frost is damaging to plants when air temperature drops below their tolerance threshold. The set of mechanisms used by cold‐tolerant plants to withstand freezing is called “hardening” and typically ...take place in autumn to protect against winter damage. The recent incorporation of a hardening scheme in the demographic vegetation model FATES opens up the possibility to investigate frost mortality to vegetation. Previously, the hardening scheme was used to improve hydraulic processes in cold‐tolerant plants. In this study, we expand upon the existing hardening scheme by implementing hardiness‐dependent frost mortality into CLM5.0‐FATES to study the impacts of frost on vegetation in temperate and boreal sites from 1950 to 2015. Our results show that the original freezing mortality approach of FATES, where each plant type had a fixed freezing tolerance threshold—an approach common to many other dynamic vegetation models, was restricted to predicting plant type distribution. The main results emerging from the new scheme are a high autumn and spring frost mortality, especially at colder sites, and increasing mid‐winter frost mortality due to global warming, especially at warmer sites. We demonstrate that the new frost scheme is a major step forward in dynamically representing vegetation in ESMs by for the first time including a level of frost tolerance that is responding to the environment and includes some level of cost (implicitly) and benefit. By linking hardening and frost mortality in a land surface model, we open new ways to explore the impact of frost events in the context of global warming.
Plain Language Summary
Frost can lead to partial or full mortality of a plant, unless it has evolved a tolerance to cold weather to avoid the formation of ice crystals in its tissues. Frost mortality is poorly represented in most advanced dynamic vegetation models, which are our primary tools for predicting climate change and to understand its effects on the biosphere. In one of those models, the functionally assembled simulator (FATES), a minimum temperature threshold is assigned to each plant type to represent the limit at which it will start to incur frost injury. In this study, we focus on making the fixed temperature threshold of FATES variable in time and space—depending on the local conditions of temperature and light. Our results show that the new frost mortality scheme can simulate autumn and spring frost mortality, also for cold‐adapted species, and increases mid‐winter frost mortality due to variable winter weather—especially at warmer sites. This is in contrast to the original frost mortality scheme, which was only applicable to predict the distribution of plant types across climate zones. The implementation presented here opens up new ways to explore the spatial evolution of frost occurrences and intensities under changing climatic conditions.
Key Points
We compare the original freezing mortality implementation in FATES (based on hard‐coded temperature thresholds) to a more dynamic approach (based on hardening)
In contrast to the original approach, a new frost scheme is able to predict the damaging effects of extreme winter events and late spring frost events
We show that autumn and spring frost mortality is large, especially at colder sites, and that mid‐winter frost mortality increases with global warming
A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such ...treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer’s disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.
•Increased NfL in CSF and blood of proteopathic neurodegenerative diseases•Increased NfL in CSF and blood coincides with onset of proteopathic lesions in brain•NfL as disease progression and treatment response marker•Translational value and predictability of current mouse models in clinical settings
Bacioglu et al. (2016) report NfL increases in CSF and blood of murine models and human α-synucleinopathies, tauopathies, and β-amyloidosis. NfL in bodily fluid constitutes a biomarker of neurodegeneration reflecting the translational value and potential impact of current mouse models in clinical settings.
Brain Aβ deposition is a key early event in the pathogenesis of Alzheimer´s disease (AD), but the long presymptomatic phase and poor correlation between Aβ deposition and clinical symptoms remain ...puzzling. To elucidate the dependency of downstream pathologies on Aβ, we analyzed the trajectories of cerebral Aβ accumulation, Aβ seeding activity, and neurofilament light chain (NfL) in the CSF (a biomarker of neurodegeneration) in Aβ-precursor protein transgenic mice. We find that Aβ deposition increases linearly until it reaches an apparent plateau at a late age, while Aβ seeding activity increases more rapidly and reaches a plateau earlier, coinciding with the onset of a robust increase of CSF NfL. Short-term inhibition of Aβ generation in amyloid-laden mice reduced Aβ deposition and associated glial changes, but failed to reduce Aβ seeding activity, and CSF NfL continued to increase although at a slower pace. When short-term or long-term inhibition of Aβ generation was started at pre-amyloid stages, CSF NfL did not increase despite some Aβ deposition, microglial activation, and robust brain Aβ seeding activity. A dissociation of Aβ load and CSF NfL trajectories was also found in familial AD, consistent with the view that Aβ aggregation is not kinetically coupled to neurotoxicity. Rather, neurodegeneration starts when Aβ seeding activity is saturated and before Aβ deposition reaches critical (half-maximal) levels, a phenomenon reminiscent of the two pathogenic phases in prion disease.
Diffuse gliomas are the most common malignant tumors of the central nervous system with poor treatment efficacy. Infiltration of immune cells into tumors during immunosurveillance is observed in ...multiple tumor entities and often associated with a favorable outcome. The aim of this study was to evaluate the infiltration of immune cells in gliomas and their association with cerebrospinal fluid (CSF) cytokine concentrations.
We applied immunohistochemistry in tumor tissue sections of 18 high-grade glioma (HGG) patients (4 anaplastic astrocytoma, IDH-wildtype WHO-III; 14 glioblastomas (GBM), IDH-wildtype WHO-IV) in order to assess and quantify leucocytes (CD45) and macrophages (CD68, CD163) within the tumor core, infiltration zone and perivascular spaces. In addition, we quantified the concentrations of 30 cytokines in the same patients' CSF and in 14 non-inflammatory controls.
We observed a significantly higher percentage of CD68
macrophages (21-27%) in all examined tumor areas when compared to CD45
leucocytes (ca. 3-7%); CD163
cell infiltration was between 5 and 15%. Compared to the tumor core, significantly more macrophages and leucocytes were detectable within the perivascular area. The brain parenchyma showing a lower tumor cell density seems to be less infiltrated by macrophages. Interleukin (IL)-7 was significantly downregulated in CSF of GBM patients compared to controls. Additionally, CD68
macrophage infiltrates showed significant correlations with the expression of eotaxin, interferon-γ, IL-1β, IL-2, IL-10, IL-13, IL-16 and vascular endothelial growth factor.
Our findings suggest that the infiltration of lymphocytes is generally low in HGG, and does not correlate with cytokine concentrations in the CSF. In contrast, macrophage infiltrates in HGG are associated with CSF cytokine changes that possibly shape the tumor microenvironment. Although results point towards an escape from immunosurveillance or even exploitation of immune cells by HGG, further studies are necessary to decipher the exact role of the immune system in these tumors.
Introduction. Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role ...of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21. Methods and Results. The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls 90% for CCL21 and 81% for CCR7 (P<0.01). In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (P<0.05) and protein expression by 24% in HMECs by oxLDL (P<0.05). Conclusions. The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques.
Introduction. Physical inactivity and obesity are independent risk factors for atherosclerosis. We analyzed the immunomodulatory capacity of 10-week intensified exercise training (ET) in obese and ...lean athletes. Markers of the innate immune response were investigated in obese (ONE: ET≤40 km/week) and lean athletes (LNE: ET≤40 km/week and LE: ET≥55 km/week). Methods. Circulating dendritic cells (DC) were analyzed by flow-cytometry for BDCA-1/-2-expression. TLR-2/-4/-7 and MyD88 were analyzed by RT-PCR and Western blot. Circulating oxLDL levels were analyzed by ELISA. Results. BDCA-1 expression at baseline was lower in ONE compared to both other groups (ONE 0.15%; LNE 0.27%; LE 0.33%; P<.05), but significantly increased in ONE after training (+50%; P<.05). In contrast, BDCA-2 expression at baseline was higher in ONE (ONE 0.25%; LNE 0.11%; LE 0.09%; P<.05) and decreased in ONE after the 10-week training period (−27%; P<.05). Gene activations of TLR-4 and TLR-7 with corresponding protein increase were found for all three groups (P<.01/P<.05) compared to pre training. A reduction of oxLDL levels was seen in ONE (−61%; P<.05). Conclusions. Intensified exercise induces an increase of BDCA-1+ DCs and TLR-4/-7 in obese athletes. We hereby describe new immune modulatory effects, which—through regular aerobic exercise—modulate innate immunity and pro-inflammatory cytokines in obesity.
This study focuses on Patagonia, where Foehn events observed in the lee of the Andes mountains are not yet well simulated by state‐of‐the‐art climate models. It has been agreed that one source of ...this shortcoming is related to the poor relief representation in models. To resolve this need, a common method used is to enhance the spatial resolution of the model to retrieve a more complex surface elevation, at the expense of calculation time or surface area covered. This paper tackles the problem from a different angle by addressing the Digital Elevation Model (DEM) generalization, that is, the altitudes generalization from a high‐resolution DEM to a coarser resolution grid model. Most current climate models use DEM generalization methods that smooth the relief, a key controlling factor in Foehn events modelling. The aim of this study is to compare three original methods of DEM generalization (percentile 90 P90, envelope maximum EM, and thalweg and crests TC) and to evaluate their impact on simulated precipitation and temperature fields on the eastern part of Patagonia, where warm and dry air masses are expected. Thanks to MAR, a Regional Climate Model, we validate the models at 10 and 5 km resolutions against the Climate Research Unit and perform three sensitivity experiments involving a change in the DEM generalization. Our results show that (a) a finer spatial resolution can slightly improve the temperature biases, however, it cannot resolve the precipitation biases and (b) a more appropriate use of DEM generalization induces a significant decrease in precipitation for the P90 and EM methods and an increase in mean temperature for all three methods in the study area. This study serves as a recommendation for a better use of DEM generalization in climate models performing in Patagonia, but also regions sharing the same orographic features as the Patagonian relief.
This work focuses on Foehn events in Patagonia which are not yet well simulated by state‐of‐the‐art climate models due to a poor relief representation. To resolve this shortcoming, a common method used in the literature is to enhance the spatial resolution of the model, at the expense of calculation time and/or surface area covered. This paper tackles the problem from a different angle by addressing the Digital Elevation Model (DEM) generalization, an important climate model feature that has received little attention so far.
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